Toluene → (1S,2R,4aS,5S,8R,8aR)-2-(acetyloxy)-5-[4-(ethyloxy)-1-methyl-4-oxobut-2-enyl]-8a-hydroxy-3,8-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate

HRID 1727172Notes

Reaction equation

HRID 1727172 reaction equation
[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:34])C=O)[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:35])[C@H:20]4[O:36][C:37](=[O:39])[CH3:38])=[O:17])[CH2:15][C@@:7]3([OH:40])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[C:41]([CH:46]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:43][CH2:44][CH3:45])=[O:42].[C:66]1(C)C=CC=CC=1>>[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:34])[CH:66]=[CH:46][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:35])[C@H:20]4[O:36][C:37](=[O:39])[CH3:38])=[O:17])[CH2:15][C@@:7]3([OH:40])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 1140TolueneHCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 86614045(1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-[1-methyl-2-oxoethyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate

Product 1

HCID 86614044(1S,2R,4aS,5S,8R,8aR)-2-(acetyloxy)-5-[4-(ethyloxy)-1-methyl-4-oxobut-2-enyl]-8a-hydroxy-3,8-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylateYield 6%

Procedure

A solution of ((1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-[1-methyl-2-oxoethyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (Preparation 141, 94 mg, 0.163 mmol) and carbethoxymethylene triphenylphosphorane (68 mg, 0.195 mmol) in anhydrous toluene (5 ml) was refluxed under nitrogen for 3 hours and then stirred at room temperature for 18 h before concentrating in vacuo. The residue was treated with sulfuric acid (10%) and extracted with two aliquots of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated in vacuo. The crude product was taken up in acetonitrile (1 ml), filtered, and purified by preparative HPLC on a Dynamex®, 5 mm×21.6 mm column, eluting with acetonitrile:water (60:40). The pure fractions were concentrated in vacuo to give the title product (7 mg, 6%).

Workup

  1. concentrationbefore concentrating in vacuo
  2. additionThe residue was treated with sulfuric acid (10%)
  3. extractionextracted with two aliquots of ethyl acetate
  4. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered
  8. custompurified by preparative HPLC on a Dynamex®, 5 mm×21.6 mm column
  9. washeluting with acetonitrile:water (60:40)
  10. concentrationThe pure fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-927fa9d746064ac4847044e06d32cf62
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

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